Manuel went under the knife just two weeks ago to have a knee procedure after some swelling was discovered in his left knee. He was kept out of the remainder of the preseason, and while Bills head coach Doug Marrone was penciling in quarterback Jeff Tuel to be the starter for the season opener, he was hoping all along that Manuel would be ready.

Ready or not, Manuel's the man.

Here's what needs to happen for the Bills to come away with a victory.

Mix Up the Play-Calls

When the Bills drafted EJ Manuel, one of the first things Marrone mentioned when asked why was his big arm.

As of yet, they haven't often tested his ability to throw deep. In fact, none of his passes have traveled more than 20 yards through the air.

A look at a diagram of Manuel's throws this preseason illustrates a significant element of the Patriots' preparation. They'll be ready for those passes, and Manuel and the Bills need to be ready to capitalize if the Patriots defensive backs sell out on quick patterns.

I told [offensive coordinator] Nathaniel [Hackett], "Let’s just make sure we get some go's. That’s what [Manuel] does best. Throw some deep balls." It was just a matter of the play-calls dictating that, not going into the game. I'm surprised that we didn't throw more go's. I think we had some other things that we were working, but I would have liked to have seen more go's.

Rhythm passes in the short-to-intermediate area are at the heart of the West Coast offense, so it should come as no surprise that most of the throws Manuel has made are of that variety. However, the Patriots were the league's worst team at defending big pass plays last season, giving up 74 plays of 20 yards or more through the air. The Bills have a ton of speed at wide receiver, with track stars like T.J. Graham (4.41 40-yard dash), Marquise Goodwin (4.27) and Robert Woods (4.51).

A big-armed quarterback and a bunch of fast receivers? It would be a disservice not to take a shot downfield.

Still, the Bills need to be judicious about it.

Known as a "bend-don't-break" defense, the Patriots would rather not give up big plays. They tightened up toward the end of the 2012 season, allowing 32 pass plays of 20 yards or more in the final eight games of the season.

Clearly, it's about more than just chucking it downfield.

Play It Safe

Playing it safe fits on both a physical and a performance level.

Manuel is known for using his legs to extend plays or to run through the heart of a defense. His ability to do both of those things could be hindered if his knee is less than 100 percent.

According to Mark Gaughan of the Buffalo News, Marrone says Manuel is "110 percent," but it wouldn't be a surprise if he's not fully comfortable with his knee just yet. He may not just have trouble with his mobility, but also in stepping into his throws.

The best thing he can do is just play within the offense, at least until he has a chance to test his knee out. That being said, injuries are simply one of the risks that come with a mobile quarterback.

Who knows if his knee is any more or less prone to injury so soon after a surgery, but it's important for Buffalo to have its franchise quarterback for as close to a full 16 games as possible. Manuel needs to play it safe and not try to do too much as a runner, but he also needs to not force the issue in the passing game.

The Patriots have preyed on turnovers for years, grabbing 20 interceptions last year, the fifth most in the league. Their ball-hawking secondary would love for Manuel to try to fit it into tight windows when he shouldn't or to make a bad read on their defense.

That brings me to the final thing Manuel can do to ensure success—or at least to avoid failure.

The Patriots defense is known for their tendency to disguise coverage, which can make life difficult for a rookie quarterback who's never faced such looks before.

Manuel was not highly regarded for his ability to make great pre-snap reads, checks and adjustments at the line of scrimmage. He's going to have to do it at some point.

If the Patriots don't do a good job of disguising their coverage, Manuel should have the confidence to make that read and attack the secondary accordingly. That being said, if there's any doubt in Manuel's mind as to what the coverage will be, or if the defense shows a look that favors the run, he can't forget who's behind him—or next to him, in the shotgun—at running back.

That would be C.J. Spiller.

There should be no shame in a heavy dose of Spiller.

The Patriots defense allowed just 3.9 yards per rush attempt in 2012, which ranked sixth in the NFL. Spiller was still able to pick up 169 total yards against the Patriots in two games, averaging 6.1 YPA. That's slightly higher than his average in 2012.

Just as important as anything Manuel could do to help the Bills in the passing game, the Bills need to be able to run the ball effectively against the Patriots front seven.

Spiller has shown the ability to make New England defenders miss plenty of times in the past, as on this reception in the fourth quarter. It was a short pass, but Spiller was able to break it for a 25-yard gain.

Quarterback Ryan Fitzpatrick lined up in the pistol formation, a modified version of the shotgun that has the quarterback a shorter distance from the center than in the shotgun (hence pistol) and the running back lined up behind the quarterback.

Fitzpatrick faked the handoff to Spiller, then the end-around to wide receiver Brad Smith. That's when he threw the ball to Spiller out in space. Only one problem: He wasn't out in space.

Three defenders circled Spiller, but the slippery running back pulled his best Houdini act to escape their clutches, juking linebacker Jerod Mayo to the ground before outrunning two defensive backs to the edge.

In a blink, Spiller found open space and picked up big yards.

Quite frankly, the more often Spiller gets the ball, the more opportunities he gets to make onlookers and Patriots defenders say, "How did he do that?!"